The technology described in this patent document relates generally to systems and methods for acquiring signals through electronic devices in the presence of confounding signals that saturate the acquisition mechanism. More particularly, the technology relates to electrodes that are used to both generate a signal in media and record the resulting signals from the media in order to identify a response of interest. The technology described in this patent document is specifically well-suited to acquire electrical signals from biological tissues and cells after an electrical stimulation signal has been applied to the same or adjacent electrodes.
There are multiple instances in which sensors are saturated by their own signals. In the case of sonar, the minimum measurable distance is related to the residual ringing of transducers after stimulation. In the case of radar, amplifiers connected to antennas can be saturated due to resonant elements or multiple nearby targets. In the case of optical diodes there will be residual charge left in the junction that would alter the diode characteristics until discharged. In the case of electrodes, amplifiers will be saturated by residual charge remaining after applying a stimulus.
The common factor in all these cases is that a signal of considerable magnitude must be applied to the transduction element (that either acts both as a signal source and as a sensor or is part of a group of sensing elements in close proximity), while the signal to be measured is of a much smaller magnitude. Such large magnitude applied signals may be necessary to generate measurable responses or to achieve a desired range as signals rapidly decay with distance.
In the specific case of neural tissues hundreds of millivolts are required to achieve a response through extracellular electrodes, while the same electrodes will show signals in the tens of microvolts when the tissues generate a signal. This four-order-of-magnitude signal disparity, and its remaining effects on the electrode, will make signal recovery impossible unless a recovery technique, as the one presented herein, is used. Such interference is commonly referred to as an ‘artifact’, a term that includes the saturation of the signal amplifying elements and its effects in the signal processing chain, as well as the remaining disturbances that are present during the signal chain recovery period. The distinction between saturation and its after effects is made, because it is desired to completely eliminate or considerably reduce the saturation period, during which there is no possibility of recovering a signal. Other techniques may be used to further reduce artifacts once the signal chain is out of saturation.
The ability to measure direct responses from stimulated elements, and thus to record signals that were previously obscured by using those elements as a source, would enhance or enable use of closed loop control techniques in which the input and output of the system, biological or otherwise, share common elements. Techniques such as those of U.S. Pat. Nos. 20,050,282,149 and 6,114,164 can be enhanced by using the techniques herein described.
Literature and commercial systems present methods for stimulation and recording without interference from stimulation artifacts, usually at the expense of functionality. In the simplest method, an experimenter must designate electrodes as stimulation or recording sites for the duration of the experiment, thus sidestepping the problem of recording at the site of the largest artifacts. Often, electronics designers place sample and hold (S/H) circuitry at the input of the recording amplifier to prevent saturation of the electronic system during stimulation (see J. L. Novak and B. C. Wheeler, “Multisite hippocampal slice recording and stimulation using a 32 element microelectrode array,” J. Neurosci. Meth., vol. 23, no. 2, pp. 239-247, March 1988, and C. A. Thomas, Jr., P. A. Springer, G. E. Loeb, Y. Berwald-Netter, and L. M. Okun, “A miniature microelectrode array to monitor the bioelectric activity of cultured cells,” Exptl. Cell Res., vol. 74, no. 1, pp. 61-66, 1972).
Another common technique is to blank, or disable, recording amplifiers near stimulation sites for 100 ms or more after stimulation (see D. T. O'Keeffe, G. M. Lyons, A. E. Donnelly, and C. A. Byrne, “Stimulus artifact removal using a software-based two-stage peak detection algorithm,” J. Neurosci. Meth., vol. 109, no. 2, pp. 137-145, August 2001). Many techniques focus on post-processing to filter out stimulation artifacts from neighboring electrodes (see J. W. Gnadt, S. D. Echols, A. Yildirim, H. Zhang, and K. Paul, “Spectral cancellation of microstimulation artifact for simultaneous neural recording In Situ,” IEEE Trans. Biomed. Eng., vol. 50, no. 10, pp. 1129-1135, October 2003, D. A. Wagenaar and S. M. Potter, “Real-time multi-channel stimulus artifact suppression by local curve fitting,” J. Neurosci. Meth., vol. 120, no. 2, pp. 17-24, October 2002, and US Patent Application 20050277844 of Strother et al.) or the same electrode (U.S. Pat. No. 7,089,049 of Kerver et al.).
These approaches all concede the data closest to the stimulation, both temporally and spatially, as lost to the stimulation artifact. However, these data may represent the most significant response to the stimulation.
An alternative approach for reducing interference from stimulation artifacts is to return the stimulation electrode to its pre-stimulation voltage immediately after stimulation through an open-loop circuit (see Y. Jimbo, N. Kasai, K. Torimitsu, T. Tateno, and H. Robinson, “A system for MEA-based multisite stimulation,” IEEE Trans. Biomed. Eng., vol. 50, no. 2, pp. 241-248, February 2003). This approach provides stimulation while reducing the artifact, both at neighboring electrodes and at the stimulation electrode. However, a difficulty with this system is that, should neuronal activity or noise occur immediately before the start of a stimulation pulse, the sample and hold circuit would store a voltage that does not correspond to the actual electrode offset.
The approach described herein is different as it makes the measuring element itself part of the compensation system, and by using feedback to return the measuring system to a useful range, can compensate for effects that an open-loop system cannot. The technique described herein can be combined with existing signal processing techniques such as those discussed in the above paragraphs to further improve the recovery speed.
Accordingly, there is a need, and it would advance the state-of-the-art, to have apparatus and methods for acquiring signals from electronic devices in the presence of confounding signals that saturate the acquisition mechanism. There is also a need for improved stimulation and recording apparatus and methods for use with electrodes that are used to generate a signal in media and record the resulting signals from the media in order to identify a response of interest. There is also a need, and it would advance the state-of-the-art, to have apparatus and methods for use in acquiring electrical signals from biological tissues and cells that reduces or eliminates artifacts in order to identify a response of interest, and that may be advantageously embodied in an integrated circuit